The long term objective of the present proposal is to determine the mechanism by which acetylcholine (ACh) produces renal vasodilation, natriuresis, and diuresis in the dog. Previous studies have shown that renal arterial infusion of ACh in control dogs produced a sustained renal vasodilation, whereas in dogs pretreated with Indomethacin (Indo), an inhibitor of prostaglandin (PG) synthetase, ACh produced an initial vasodilation followed by a profound renal vasoconstriction. Recently, we have observed that renal arterial infusion of a low dose of atropine, a non-specific muscarinic receptor blocker, prevented the renal vasoconstriction, whereas a high dose of atropine prevented the renal vasodilation by ACh in Indo-treated dogs. These observations suggest that the renal vasodilator and vasoconstrictor effect may be mediated by two different muscarinic receptors. One of the specific aims of the present proposal is to determine the role of different muscarinic receptors in the renal vasoconstriction and vasodilation produced by ACh in Indo-treated dogs. This would be done by the renal arterial infusion of specific muscarinic receptor blockers before and during the infusion of ACh in Indo-treated dogs. Since ACh is also known to stimulate the formation of cGMP, PGI2 and cAMP in the renal vasodilatory response to ACh. This would be done by the determination of renal excretion of cGMP, PGI2, and cAMP before and during the infusion of ACh in control and Indo- treated dogs. Furthermore, the role of the EDRF-nitric oxide-cGMP system and PGI2-cAMP in the renal vasodilatory response to ACh would also be examined in control and Indo-treated dogs receiving an intrarenal infusion of N-monomethyl-L-arginine an inhibitor of nitric oxide synthesis. Information about why blockade of PG synthesis predisposes to renal vasoconstriction may increase our understanding of the nature of the impairment in renal function that occurs in certain clinical disorders when PG synthetase inhibitors are given.

Project Start
Project End
Budget Start
Budget End
Support Year
26
Fiscal Year
1996
Total Cost
Indirect Cost
Faruque, Mezbah U; Chen, Guanjie; Doumatey, Ayo P et al. (2017) Transferability of genome-wide associated loci for asthma in African Americans. J Asthma 54:1-8
Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing et al. (2017) Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome. Sci Rep 7:46398
Kessler, Michael D; Yerges-Armstrong, Laura; Taub, Margaret A et al. (2016) Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nat Commun 7:12521
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Rand, Kristin A; Rohland, Nadin; Tandon, Arti et al. (2016) Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk. Hum Mol Genet 25:371-81
Mathias, Rasika Ann; Taub, Margaret A; Gignoux, Christopher R et al. (2016) A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome. Nat Commun 7:12522
Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184
Kurian, P; Dunston, G; Lindesay, J (2016) How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. J Theor Biol 391:102-12
Ogunjirin, Adebowale E; Fortunak, Joseph M; Brown, LaVerne L et al. (2015) Competition, Selectivity and Efficacy of Analogs of A-84543 for Nicotinic Acetylcholine Receptors with Repositioning of Pyridine Nitrogen. Neurochem Res 40:2131-42
Winchester, Danyelle; Ricks-Santi, Luisel; Mason, Tshela et al. (2015) SPINK1 Promoter Variants Are Associated with Prostate Cancer Predisposing Alterations in Benign Prostatic Hyperplasia Patients. Anticancer Res 35:3811-9

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